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1. LBA11 Alectinib (ALC) vs crizotinib (CRZ) in Asian patients (pts) with treatment-naïve advanced ALK+ non-small cell lung cancer (NSCLC): 5-year update from the phase III ALESIA study

Author

Zhou, C., primary, Lu, Y., additional, Kim, S-W., additional, Baisamut (Reungwetwattana), T., additional, Zhou, J., additional, Zhang, Y., additional, He, J., additional, Yang, J., additional, Cheng, Y., additional, Lee, S-H., additional, Chang, J., additional, Fang, J., additional, Liu, Z., additional, Bu, L., additional, Qian, L., additional, Xu, T., additional, Archer, V., additional, Hilton, M., additional, Zhou, M., additional, and Zhang, L., additional

Published
2022
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2. 03. Is ethnicity an appropriate measure of health care marginalization?: A systematic review and meta-analysis of the outcomes of diabetic foot ulceration in the Aboriginal population

Author

Johnson, G., Vergis, A., Unger, B., Park, J., Gillman, L., Hickey, K., Pace, D., Azin, A., Guidolin, K., Lam-Tin-Cheung, K., Chadi, S., Quereshy, F., Catton, J., Rubin, B., Bell, J., Marangos, J., Heesters, A., Stuart-McEwan, T., Shariff, F., Wright, F., Ahmed, N., Nadler, A., Hallet, J., Gentles, J., Chen, L., Hwang, H., Parapini, M., Hirpara, D., Sidhu, R., Scott, T., Karimuddin, A., Guo, R., Nguyen, A., Osborn, J., Wiseman, S., Nabata, K., Ertel, E., Lenet, T., Baker, L., Park, L., Vered, M., Zahrai, A., Shorr, R., Davis, A., McIsaac, D., Tinmouth, A., Fergusson, D., Martel, G., Rummel, S., Stefic-Cubic, M., Stewart, M., Melck, A., McKechnie, T., Anpalagan, T., Ichhpuniani, S., Lee, Y., Ramji, K., Eskicioglu, C., Zhu, A., Deng, S., Greene, B., Tsang, M., Palter, V., Jayaraman, S., Mann, A., Tittley, J., Cadeddu, M., Nguyen, M., Madani, A., Pasternak, J., Hong, D., Qu, L., Istl, A., Tang, E., Gray, D., Zuckerman, J., Coburn, N., Callum, J., McLeod, R., Pearsall, E., Lin, Y., Turgeon, A., Mahar, A., Kammili, A., Kriviraltcheva-Kaneva, P., Lee, L., Cools-Lartigue, J., Ferri, L., Mueller, C., Haas, B., Tillman, B., Guttman, M., Chesney, T., Zuk, V., Hsu, A., Chan, W., Vasdev, R., D’Souza, K., Huynh, C., Ling, L. Cadili J., Warburton, R., Hameed, M., Glass, L., Williamson, H., Murphy, P., Leslie, K., Hawel, J., Kerr, L., Zablotny, S., Roldan, H., He, W., Jiang, X., Zheng, B., Fiore, J., Feldman, L., Fried, G., Valanci, S., Balvardi, S., Cipolla, J., Kaneva, P., Demyttenaere, S., Boutros, M., Alhashemi, M., Miles, A., Purich, K., Verhoeff, K., Shapiro, J., Bigam, D., Kung, J., Fecso, A., Mosko, J., Skubleny, D., Hamilton, P., Ghosh, S., Widder, S., Schiller, D., Do, U., El Kefraoui, C., Pook, M., Barone, N., Montgomery, H., Nguyen-Powanda, P., Rajabiyazdi, F., Elhaj, H., Lapointe-Gagner, M., Olleik, G., Antoun, A., Safa, N., Di Lena, E., Meterissian, S., Meguerditchian, A., Lee, F., Baldini, G., Serrano Aybar, P.E., Parpia, S., Ruo, L., Tywonek, K., Lee, S., O’Neill, C., Faisal, N., Alfayyadh, A., Gundayao, M., Meyers, B.M., Habashi, R., Kruse, C., Levin, M., Aldrich, K., Grantcharov, T., Langerman, A., Forbes, H., Anantha, R., Fawcett, V., Hetherington, A., Pravong, V., Gervais, M., Rakovich, G., Selvam, R., Hu, R., Musselman, R., Raiche, I., Moloo, H., Liu, R., Elnahas, A., Alkhamesi, N., Alnumay, A., Schlachta, C., Walser, E., Zhang, C., Cristancho, S., Ott, M., Lee, A., Niu, B., Balaa, F., Gawad, N., Ren, K., Qiu, Y., Hamann, K., How, N., Leveille, C., Davidson, A., Eqbal, A., Sardiwalla, Y., Korostensky, M., Lee, E., Yang, I., Muaddi, H., Stukel, T., de Mestral, C., Nathens, A., Karanicolas, P., Frigault, J., Lemieux, S., Breton, D., Bouchard, P., Bouchard, A., Grégoire, R., Letarte, F., Bouchard, G., Drolet, S., Avoine, S., Gagné, J., Thibault, C., Jutras Bouthillette, N., Gosselin, M., Rosenzveig, A., Stuleanu, T., Jarrar, A., Kolozsvari, N., Skelhorne-Gross, G., Nenshi, R., Jerath, A., Gomez, D., Singh, K., Amir, T., Liu, E., Farquharson, S., Mao, R., Lan, L., Yan, J., Allard-Coutu, A., Mierzwa, A., Tin, R., Brisebois, R., Bradley, N., Wigen, R., Hartford, L., Van Koughnett, J., Vogt, K., Hilsden, R., Parry, N., Allen, L., Raskin, R., Jones, J., Neumann, K., Dwyer, C., Strickland, M., O’Dochartaigh, D., Lobay, K., Kabaroff, A., Chang, E., Sun, W., Beck, J., Davidson, J., Jones, S., Van Hooren, T., Schmitz, E., El Hafid, M., Dang, J., Mocanu, V., Lutzak, G., Sultanian, R., Wong, C., Karmali, S., Petrera, M., Pickell, M., Auer, R., Patro, N., Li, B., Wilson, H., Jogiat, U., Switzer, N., Li, C., Al Hinai, A., Cieply, A., Hawes, H., Joos, E., Saleh, A., Engels, P., Drung, J., Pang, G., Kwong, M., Ellsmere, J., Chang, D., Hutter, M., Spence, R., Abou Khalil, M., Vasilevsky, C., Morin, N., Longtin, Y., Liberman, S., Montpetit, P., Poirier, M., Mukherjee, K., Sebajang, H., Younan, R., Schwenter, F., De Broux, E., Larsen, K., Beckett, A., Nantais, J., Kay, J., Lohre, R., Ayeni, O., Goel, D., de SA, D., He, R., Hylton, D., Bedard, E., Johnson, S., Laing, B., Valji, A., Hanna, W., Turner, S., Akhtar-Danesh, G., Akhtar-Danesh, N., Shargall, Y., Gupta, V., Kidane, B., Limbachia, J., Sullivan, K., Farrokhyar, F., Leontiadis, G., Patel, Y., Churchill, I., Xie, F., Seely, A., Spicer, J., Yasufuku, K., Beauchamp, M., Wald, J., Mbuagbaw, L., Agzarian, J., Finley, C., Fahim, C., Abbas, M., Olaiya, O., Begum, H., Ednie, A., Palma, D., Warner, A., Malthaner, R., Fortin, D., Qiabi, M., Nayak, R., Nguyen, T., Louie, A., Rodrigues, G., Yaremko, B., Laba, J., Inculet, R., Alaichi, J., Mador, B., Lai, H., White, J., Kim, M., Darling, G., Rousseau, M., Samarasinghe, Y., Lee, M., Thiru, L., Levine, O., Juergens, R., Brogly, S., Li, W., Lougheed, D., Petsikas, D., Mistry, N., Gatti, A., Abdul, S., Anestee, C., Gilbert, S., Sundaresan, S., Villeneuve, P., Maziak, D., Razzak, R., Ashrafi, A., Tregobov, N., Hassanzadeh, N., Stone, S., Panjwani, A., Bong, T., Bond, R., Hafizi, A., De Meo, M., Rayes, R., Milette, S., Vagai, M., Usatii, M., Chandrasekaran, A., Giannias, B., Bourdeau, F., Sangwan, V., Bertos, N., Moraes, C., Huang, S., Quail, D., Walsh, L., Camilleri-Broet, S., Fiset, P., Bilgic, E., Quaiattini, A., Maurice-Ventouris, M., Najmeh, S., Esther, L., Lu, J., Malhan, R., Brophy, S., Brennan, K., French, D., Resende, V., Momtazi, M., Solaja, O., Sisson, D., Donahoe, L., Bedard, P., Hansen, A., De Perrot, M., Alghamedi, A., Simone, A., Huang, J., Murthy, S., Lin, J., Li, H., Crowther, M., Linkins, L., Lau, E., Schneider, L., Douketis, J., Greenberg, B., Allen-Avodabo, C., Davis, L., Zhao, H., Sirois, C., Mulder, D., Al Rawahi, A., Aftab Abdul, S., Nguyen, D., Anstee, C., Delic, E., Sasewich, H., Islam, T., Low, D., Humer, M., Le Nguyen, D., Kay, M., Shayegan, B., Adili, A., Kaafarani, M., Chouiali, F., Muthukrishnan, N., Maleki, F., Ovens, K., Gold, M., Sorin, M., Falutz, R., Forghani, R., Hunka, N., Kennedy, R., Bigsby, R., Bharadwaj, S., Gowing, S., Pearce, K., Jones, D., Kumar, S., Gingrich, M., Ahmadzai, Z., Thavorn, K., Namavarian, A., Mohammed, A., Uddin, S., Behzadi, A., Brar, A., Peters, E., Buduhan, G., Tan, L., Srinathan, S., Levy, J., Ringash, J., Sutradhar, R., Robinson, M., Bednarek, L., Wang, H., MacDonald, D., Graham, K., Enns, S., Tan, A., Bruinooge, A., Poole, E., Pascoe, C., Karakach, T., Halayko, A., Fang, B., Birch, D., Singh, H., Hershorn, O., Hochman, D., Helewa, R., Robertson, R., Cahill, C., Lipson, M., Afzal, A., Maclean, A., Roen, S., Buie, W., Chu, M., Amin, N., Jaffer, H., Rebello, R., Doumouras, A., Hajjar, R., Oliero, M., Cuisiniere, T., Fragoso, G., Calvé, A., Djediai, S., Annabi, B., Richard, C., Santos, M., Zhou, Y., Dodd), S., Ring, B., Yuan, Y., Garfinkle, R., Dell’Aniello, S., Bhatnagar, S., Ghitulescu, G., Faria, J., Brassard, P., Salama, E., Amar-Zifkin, A., Talwar, G., Daniel, R., AlSulaim, H., Alqahtani, M., Al-Masrouri, S., Chen, A., Patel, A., Brissette, V., Al Busaidi, N., Moon, J., Demian, M., MacRae, H., Alam, F., Holland, J., Cwintal, M., Rigas, G., Pang, A., Marinescu, D., Brown, C., Raval, M., Phang, P., Ghuman, A., Li, M., Muncner, S., Mihajlovic, I., Dykstra, M., Snelgrove, R., Monton, O., Smith, A., AlAamer, O., AlSelaim, N., AlMalki, M., Al-osail, A., Ruxton, R., Manuel, P., Mohamed, F., Motamedi, M.K., Serahati, S., Rajendran, L., Phang, T., Caminsky, N., Alavi, K., Paquette, I., MacLean, T., Wexner, S., Steele, S., Patel, S., Bordeianou, L., Sylla, P., Bayat, Z., Kennedy, E., Victor, C., Govindarajan, A., Liang, J., Roy, H., Baig, Z., Karimmudin, A., Gill, D., Ginther, N., Alrashid, F., Wiseman, V., Zhang, L., MacDonald, P., Merchant, S.M., Wattie Barnett, K., Caycedo-Marulanda, A., Patel, S.V., Harra, Z., Hegagi, M., Alghaithi, N., Papillon, E., Kasteel, N., Kaur, G., Bindra, S., Malhotra, A., Graham, C., MacLean, A., Beck, P., Jijon, H., Ferraz, J., Szwimer, R., Merchant, S., Kong, W., Gyawali, B., Hanna, T., Chung, W., Nanji, S., Booth, C., Li, V., Awan, A., Serrano, P., Jacobson, M., Chanco, M., Wen, V., Singh, N., Peiris, L., Pasieka, J., Ghatage, P., Buie, D., Bouchard-Fortier, A., Mack, L., Marini, W., Zheng, W., Swallow, C., Reedijk, M., DiPasquale, A., Prus-Czrnecka, Z., Delmar, L., Gagnon, N., Villiard, R., Martel, É., Cadrin-Chênevert, A., Ledoux, É., Racicot, C., Mysuria), S., Bazzarelli, A., Pao, J., Zhang, M., McKevitt, E., Kuusk, U., Van Laeken, N., Bovill, E., Isaac, K., Dingee, C., Hunter-Smith, A., Cuthbert, C., Fergus, K., Barbera, L., Efegoma, Y., Howell, D., Isherwood, S., Levasseur, N., Scheer, A., Simmons, C., Srikantham, A., Temple-Orberle, C., Xu, Y., Metcalfe, K., Quan, M., Alqaydi, A., la, J., Digby, G., Brind’Amour, A., Sidéris, L., Dubé, P., De Guerke, L., Fortin, S., Auclair, M., Trilling, B., Tremblay, J., Di Lena, É., Hopkins), B., Wong, S., Hopkins, B., Dumitra, S., Mysuria, S., Kapur, H., Bazarelli, A., Cadili, L., DeGirolamo, K., Ng, D., Ali, A., Eymae, D., Lee, K., Brar, S., Conner, J., Magalhaes, M., Allen, K., Baliski, C., Cyr, D., Sari, A., Messenger, D., Driman, D., Assarzadegan, N., Juda, A., Brar, M., Kirsch, R., Lamontagne, A., Gamache, Y., Mardinger, C., Lee, C., Duckworth, R., Brindle, M., Fraulin, F., Austen, L., Kortbeek, J., Hyndman, M., Jamjoum, G., Langer, S., Yuan Xu, Y., Kong, S., Lim, D., Retrouvey, H., Kerrebijn, I., Butler, K., O’Neill, A., Cil, T., Zhong, T., Hofer, S., McCready, D., Look Hong, N., Skipworth, J., Mah, A., Desai, S., Chung, S., Scudamore, C., Segedi, M., Vasilyeva, E., Li, J., Kim, P., Deprato, A., Dajani, K., Gilbert, R., Smoot, R., Tzeng, C., Rocha, F., Yohanathan, L., Cleary, S., Bertens, K., Reyna-Sepulveda, F., Badrudin, D., Gala-Lopez, B., Hanna, N., Wei, X., Kaliwal, Y., Wei, A., Henault, D., Barrette, B., Pelletier, S., Thebault, P., Beaudry-Simoneau, E., Rong, Z., Plasse, M., Dagenais, A. Roy M., Létourneau, R., Lapointe, R., Vandenbroucke-Menu, F., Nguyen, B., Soucy, G., Turcotte, S., Lemke, M., Waugh, E., Quan, D., Skaro, A., Lund, M., Glinka, J., Jada, G., Daza, J., Msallak, H., Zhang, B., Workneh, A., Faisal, S., Faisal, R., Fabbro, M., Gu, C., Claassen, M., Sapisochin, G., Breadner, D., Welch, S., Webb, A., Lester, E., Shapiro, A., Eurich, D., Essaji, Y., Shrader, H., Nayyar, A., Suraju, M., Williams-Perez, S., Ear, P., Chan, C., Smith, V., Rivers-Bowerman, M., Costa, A., Stueck, A., Campbell, N., Allen, S., Mir, Z., Golding, H., McKeown, S., Flemming, J., Groome, P., Djerboua, M., Elbekri, S., Girard, E., Morency-Potvin, P., Dagenais, M., Roy, A., Letourneau, R., Simoneau, E., Zuker, N., Oakley, M., Chartrand, G., Misheva, B., Bendavid, Y., Melland-Smith, M., Smith, L., Tan, J., Kahn, U., McLean, C., Fortin, M., Paré, X., Doyon, A., Keshavjee, S., Schwenger, K., Yadav, J., Fischer, S., Jackson, T., Allard, J., Okrainec, A., Anvari, S., Lovrics, O., Aditya, I., Khondker, A., Walsh, M., Hardy, K., Romanescu, R., Deaninck, F., Linton, J., Fowler-Woods, M., Fowler-Woods, A., Shingoose, G., Zmudzinski, M., Cloutier, Z., Archer, V., Shiroky, J., Abu Halimah, J., Boudreau, V., Marcil, G., Hardy-Henry, A., Lin, W., Hagen, J., and Connell, M.

Subjects
Abstracts, Canadian Association of General Surgeons, Canadian Hernia Society, Canada, Canadian Association of Thoracic Surgeons, Canadian Hepato-Pancreato-Biliary Association, Humans, Canadian Society of Surgical Oncology, Canadian Association of Bariatric Physicians and Surgeons, Canadian Society of Colon and Rectal Surgeons
Published
2022

3. 2021 Canadian Surgery Forum01. Design and validation of a unique endoscopy simulator using a commercial video game03. Is ethnicity an appropriate measure of health care marginalization?: A systematic review and meta-analysis of the outcomes of diabetic foot ulceration in the Aboriginal population04. Racial disparities in surgery — a cross-specialty matched comparison between black and white patients05. Starting late does not increase the risk of postoperative complications in patients undergoing common general surgical procedures06. Ethical decision-making during a health care crisis: a resource allocation framework and tool07. Ensuring stability in surgical training program leadership: a survey of program directors08. Introducing oncoplastic breast surgery in a community hospital09. Leadership development programs for surgical residents: a review of the literature10. Superiority of non-opioid postoperative pain management after thyroid and parathyroid operations: a systematic review and meta-analysis11. Timing of ERCP relative to cholecystectomy in patients with ductal gallstone disease12. A systematic review and meta-analysis of randomized controlled trials comparing intraoperative red blood cell transfusion strategies13. Postoperative outcomes after frail elderly preoperative assessment clinic: a single-institution Canadian perspective14. Selective opioid antagonists following bowel resection for prevention of postoperative ileus: a systematic review and meta-analysis15. Peer-to-peer coaching after bile duct injury16. Laparoscopic median arcuate ligament release: a video abstract17. Retroperitoneoscopic approach to adrenalectomy19. Endoscopic Zenker diverticulotomy: a video abstract20. Variability in surgeons’ perioperative management of pheochromocytomas in Canada21. The contribution of surgeon and hospital variation in transfusion practice to outcomes for patients undergoing elective gastrointestinal cancer surgery: a population-based analysis22. Perioperative transfusions for gastroesophageal cancers: risk factors and short- and long-term outcomes23. The association between frailty and time alive and at home after cancer surgery among older adults: a population-based analysis24. Psychological and workplace-related effects of providing surgical care during the COVID-19 pandemic in British Columbia, Canada25. Safety of venous thromboembolism prophylaxis in endoscopic retrograde cholangiopancreatography: a systematic review26. Complications and reintervention following laparoscopic subtotal cholecystectomy: a systematic review and meta-analysis27. Synchronization of pupil dilations correlates with team performance in a simulated laparoscopic team coordination task28. Receptivity to and desired design features of a surgical peer coaching program: an international survey9. Impact of the COVID-19 pandemic on rates of emergency department utilization due to general surgery conditions30. The impact of the current COVID-19 pandemic on the exposure of general surgery trainees to operative procedures31. Association between academic degrees and research productivity: an assessment of academic general surgeons in Canada32. Laparoscopic endoscopic cooperative surgery (LECS) for subepithelial gastric lesion: a video presentation33. Effect of the COVID-19 pandemic on acute care general surgery at an academic Canadian centre34. Opioid-free analgesia after outpatient general surgery: a pilot randomized controlled trial35. Impact of neoadjuvant immunotherapy or targeted therapies on surgical resection in patients with solid tumours: a systematic review and meta-analysis37. Surgical data recording in the operating room: a systematic review of modalities and metrics38. Association between nonaccidental trauma and neighbourhood socioeconomic status during the COVID-19 pandemic: a retrospective analysis39. Laparoscopic repair of a transdiaphragmatic gastropleural fistula40. Video-based interviewing in medicine: a scoping review41. Indocyanine green fluorescence angiography for prevention of anastomotic leakage in colorectal surgery: a cost analysis from the hospital payer’s perspective43. Perception or reality: surgical resident and faculty assessments of resident workload compared with objective data45. When illness and loss hit close to home: Do health care providers learn how to cope?46. Remote video-based suturing education with smartphones (REVISE): a randomized controlled trial47. The evolving use of robotic surgery: a population-based analysis48. Prophylactic retromuscular mesh placement for parastomal hernia prevention: a retrospective cohort study of permanent colostomies and ileostomies49. Intracorporeal versus extracorporeal anastomosis in laparoscopic right hemicolectomy: a retrospective cohort study on anastomotic complications50. A lay of the land — a description of Canadian academic acute care surgery models51. Emergency general surgery in Ontario: interhospital variability in structures, processes and models of care52. Trauma 101: a virtual case-based trauma conference as an adjunct to medical education53. Assessment of the National Surgical Quality Improvement Program Surgical Risk Calculator for predicting patient-centred outcomes of emergency general surgery patients in a Canadian health care system54. Sustainability of a narcotic reduction initiative: 1 year following the Standardization of Outpatient Procedure (STOP) Narcotics Study55. Barriers to transanal endoscopic microsurgery referral56. Geospatial analysis of severely injured rural patients in a geographically complex landscape57. Implementation of an incentive spirometry protocol in a trauma ward: a single-centre pilot study58. Impostor phenomenon is a significant risk factor for burnout and anxiety in Canadian resident physicians: a cross-sectional survey59. Understanding the influence of perioperative education on performance among surgical trainees: a single-centre experience60. The effect of COVID-19 pandemic on current and future endoscopic personal protective equipment practices: a national survey of 77 endoscopists61. Case report: delayed presentation of perforated sigmoid diverticulitis as necrotizing infection of the lower limb62. Investigating disparities in surgical outcomes in Canadian Indigenous populations63. Fundoplication is superior to medical therapy for Barrett esophagus disease regression and progression: a systematic review and meta-analysis64. Development of a novel online general surgery learning platform and a qualitative preimplementation analysis65. Hagfish slime exudate as a potential novel hemostatic agent: developing a standardized assessment protocol66. The effect of the first wave of the COVID-19 pandemic on surgical oncology case volumes and wait times67. Safety of same-day discharge in high-risk patients undergoing ambulatory general surgery68. External validation of the Codman score in colorectal surgery: a pragmatic tool to drive quality improvement69. Improved morbidity and gastrointestinal restoration rates without compromising survival rates for diverting loop ileostomy with colonic lavage versus total abdominal colectomy for fulminant Clostridioides difficile colitis: a multicentre retrospective cohort study70. Potential access to emergency general surgical care in Ontario71. Immersive virtual reality (iVR) improves procedural duration, task completion and accuracy in surgical trainees: a systematic review01. Clinical validation of the Canada Lymph Node Score for endobronchial ultrasound02. Venous thromboembolism in surgically treated esophageal cancer patients: a provincial population-based study03. Venous thromboembolism in surgically treated lung cancer patients: a population-based study04. Is frailty associated with failure to rescue after esophagectomy? A multi-institutional comparative analysis of outcomes05. Routine systematic sampling versus targeted sampling of lymph nodes during endobronchial ultrasound: a feasibility randomized controlled trial06. Gastric ischemic conditioning reduces anastomotic complications in patients undergoing esophagectomy: a systematic review and meta-analysis07. Move For Surgery, a novel preconditioning program to optimize health before thoracic surgery: a randomized controlled trial08. In case of emergency, go to your nearest emergency department — Or maybe not?09. Does preoperative SABR increase the risk of complications from lung cancer resection? A secondary analysis of the MISSILE trial10. Segmental resection for lung cancer: the added value of near-infrared fluorescence mapping diminishes with surgeon experience11. Toward competency-based continuing professional development for practising surgeons12. Stereotactic body radiotherapy versus surgery in older adults with NSCLC — a population-based, matched analysis of long-term dependency outcomes13. Role of adjuvant therapy in esophageal cancer patients after neoadjuvant therapy and curative esophagectomy: a systematic review and meta-analysis14. Evaluation of population characteristics on the incidence of thoracic empyema: an ecological study15. Determining the optimal stiffness colour threshold and stiffness area ratio cut-off for mediastinal lymph node staging using EBUS elastography and AI: a pilot study16. Quality assurance on the use of sequential compression stockings in thoracic surgery (QUESTs)17. The relationship between fissureless technique and prolonged air leak for patients undergoing video-assisted thoracoscopic lobectomy18. CXCR2 inhibition as a candidate for immunomodulation in the treatment of K-RAS-driven lung adenocarcinoma19. Assessment tools for evaluating competency in video-assisted thoracoscopic lobectomy: a systematic review20. Understanding the current practice on chest tube management following lung resection among thoracic surgeons across Canada21. Effect of routine jejunostomy tube insertion in esophagectomy: a systematic review and meta-analysis22. Recurrence of primary spontaneous pneumothorax following bullectomy with pleurodesis or pleurectomy: a retrospective analysis23. Surgical outcomes following chest wall resection and reconstruction24. Outcomes following surgical management of primary mediastinal nonseminomatous germ cell tumours25. Does robotic approach offer better nodal staging than thoracoscopic approach in anatomical resection for non–small cell lung cancer? A single-centre propensity matching analysis26. Competency assessment for mediastinal mass resection and thymectomy: design and Delphi process27. The contemporary significance of venous thromboembolism (deep venous thrombosis [DVT] and pulmonary embolus [PE]) in patients undergoing esophagectomy: a prospective, multicentre cohort study to evaluate the incidence and clinical outcomes of VTE after major esophageal resections28. Esophageal cancer: symptom severity at the end of life29. The impact of pulmonary artery reconstruction on postoperative and oncologic outcomes: a systematic review30. Association with surgical technique and recurrence after laparoscopic repair of paraesophageal hernia: a single-centre experience31. Enhanced recovery after surgery (ERAS) in esophagectomy32. Surgical treatment of esophageal cancer: trends in surgical approach and early mortality at a single institution over the past 18 years34. Adverse events and length of stay following minimally invasive surgery in paraesophageal hernia repair35. Long-term symptom control comparison of Dor and Nissen fundoplication following laparoscopic para-esophageal hernia repair: a retrospective analysis36. Willingness to pay: a survey of Canadian patients’ willingness to contribute to the cost of robotic thoracic surgery37. Radiomics in early-stage lung adenocarcinoma: a prediction tool for tumour immune microenvironments38. Effectiveness of intraoperative pyloric botox injection during esophagectomy: how often is endoscopic intervention required?39. An artificial intelligence algorithm for predicting lymph node malignancy during endobronchial ultrasound40. The effect of major and minor complications after lung surgery on length of stay and readmission41. Measuring cost of adverse events following thoracic surgery: a scoping review42. Laparoscopic paraesophageal hernia repair: characterization by hospital and surgeon volume and impact on outcomes43. NSQIP 5-Factor Modified Frailty Index predicts morbidity but not mortality after esophagectomy44. Trajectory of perioperative HRQOL and association with postoperative complications in thoracic surgery patients45. Variation in treatment patterns and outcomes for resected esophageal cancer at designated thoracic surgery centres46. Patient-reported pretreatment health-related quality of life (HRQOL) predicts short-term survival in esophageal cancer patients47. Analgesic efficacy of surgeon-placed paravertebral catheters compared with thoracic epidural analgesia after Ivor Lewis esophagectomy: a retrospective noninferiority study48. Rapid return to normal oxygenation after lung surgery49. Examination of local and systemic inflammatory changes during lung surgery01. Implications of near-infrared imaging and indocyanine green on anastomotic leaks following colorectal surgery: a systematic review and meta-analysis02. Repeat preoperative endoscopy after regional implementation of electronic synoptic endoscopy reporting: a retrospective comparative study03. Consensus-derived quality indicators for operative reporting in transanal endoscopic surgery (TES)04. Colorectal lesion localization practices at endoscopy to facilitate surgical and endoscopic planning: recommendations from a national consensus Delphi process05. Black race is associated with increased mortality in colon cancer — a population-based and propensity-score matched analysis06. Improved survival in a cohort of patients 75 years and over with FIT-detected colorectal neoplasms07. Laparoscopic versus open loop ileostomy reversal: a systematic review and meta-analysis08. Posterior mesorectal thickness as a predictor of increased operative time in rectal cancer surgery: a retrospective cohort study09. Improvement of colonic anastomotic healing in mice with oral supplementation of oligosaccharides10. How can we better identify patients with rectal bleeding who are at high risk of colorectal cancer?11. Assessment of long-term bowel dysfunction in rectal cancer survivors: a population-based cohort study12. Observational versus antibiotic therapy for acute uncomplicated diverticulitis: a noninferiority meta-analysis based on a Delphi consensus13. Radiotherapy alone versus chemoradiotherapy for stage I anal squamous cell carcinoma: a systematic review and meta-analysis14. Is the Hartmann procedure for diverticulitis obsolete? National trends in colectomy for diverticulitis in the emergency setting from 1993 to 201515. Sugammadex in colorectal surgery: a systematic review and meta-analysis16. Sexuality and rectal cancer treatment: a qualitative study exploring patients’ information needs and expectations on sexual dysfunction after rectal cancer treatment17. Video-based interviews in selection process18. Impact of delaying colonoscopies during the COVID-19 pandemic on colorectal cancer detection and prevention19. Opioid use disorder associated with increased anastomotic leak and major complications after colorectal surgery20. Effectiveness of a rectal cancer education video on patient expectations21. Robotic-assisted rectosigmoid and rectal cancer resection: implementation and early experience at a Canadian tertiary centre22. An online educational app for rectal cancer survivors with low anterior resection syndrome: a pilot study23. The effects of surgeon specialization on the outcome of emergency colorectal surgery24. Outcomes after colorectal cancer resections in octogenarians and older in a regional New Zealand setting — What are the predictors of mortality?25. 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Author

Johnson, G., primary, Hickey, K., primary, Azin, A., primary, Guidolin, K., primary, Shariff, F., primary, Gentles, J., primary, Parapini, M., primary, Guo, R., primary, Ertel, E., primary, Lenet, T., primary, Nabata, K., primary, McKechnie, T., primary, Zhu, A., primary, Nguyen, M., primary, Qu, L., primary, Zuckerman, J., primary, Kammili, A., primary, D’Souza, K., primary, Glass, L., primary, Kerr, L., primary, He, W., primary, Lee, L., primary, Balvardi, S., primary, Miles, A., primary, Fecso, A., primary, Skubleny, D., primary, Do, U., primary, Serrano Aybar, P.E., primary, Kruse, C., primary, Forbes, H., primary, Pravong, V., primary, Selvam, R., primary, Liu, R., primary, Walser, E., primary, Lee, A., primary, Ren, K., primary, Muaddi, H., primary, Frigault, J., primary, Rosenzveig, A., primary, Skelhorne-Gross, G., primary, Singh, K., primary, Mierzwa, A., primary, Wigen, R., primary, Raskin, R., primary, Dwyer, C., primary, Sun, W., primary, Schmitz, E., primary, Patro, N., primary, Wilson, H., primary, Li, C., primary, Drung, J., primary, Pang, G., primary, Abou Khalil, M., primary, Larsen, K., primary, Lan, L., primary, He, R., primary, Akhtar-Danesh, G., primary, Hirpara, D., primary, Sullivan, K., primary, Jogiat, U., primary, Patel, Y., primary, Abbas, M., primary, Ednie, A., primary, Alaichi, J., primary, Turner, S., primary, Lee, Y., primary, Nayak, R., primary, Mistry, N., primary, Abdul, S., primary, Razzak, R., primary, De Meo, M., primary, Esther, L., primary, Brophy, S., primary, Resende, V., primary, Sisson, D., primary, Alghamedi, A., primary, Shargall, Y., primary, Greenberg, B., primary, Huynh, C., primary, Al Rawahi, A., primary, Humer, M., primary, Le Nguyen, D., primary, Kaafarani, M., primary, Hunka, N., primary, Churchill, I., primary, Finley, C., primary, Jones, D., primary, Gupta, V., primary, Peters, E., primary, Robinson, M., primary, Wang, H., primary, Graham, K., primary, Bruinooge, A., primary, Verhoeff, K., primary, Cahill, C., primary, Hajjar, R., primary, Purich, K., primary, Garfinkle, R., primary, Talwar, G., primary, AlSulaim, H., primary, Brissette, V., primary, Holland, J., primary, Brown, C., primary, Li, M., primary, Monton, O., primary, AlAamer, O., primary, Ruxton, R., primary, Motamedi, M.K., primary, Caminsky, N., primary, Bayat, Z., primary, Liang, J., primary, Roy, H., primary, Moon, J., primary, Salama, E., primary, Wiseman, V., primary, Harra, Z., primary, Hegagi, M., primary, Alghaithi, N., primary, Papillon, E., primary, Kasteel, N., primary, Szwimer, R., primary, Merchant, S., primary, Li, V., primary, Jacobson, M., primary, Marini, W., primary, DiPasquale, A., primary, Gagnon, N., primary, Mysuria), S., primary, Hunter-Smith, A., primary, Alqaydi, A., primary, Di Lena, É., primary, Mysuria, S., primary, Kapur, H., primary, Cadili, L., primary, Ng, D., primary, Allen, K., primary, Cyr, D., primary, Allard-Coutu, A., primary, Mardinger, C., primary, Nguyen, D., primary, Langer, S., primary, Lim, D., primary, Reyna-Sepulveda, F., primary, Hanna, N., primary, Henault, D., primary, Lemke, M., primary, Lund, M., primary, Park, L., primary, Glinka, J., primary, Waugh, E., primary, Webb, A., primary, Essaji, Y., primary, Shrader, H., primary, Smith, V., primary, Gilbert, R., primary, Mir, Z., primary, Elbekri, S., primary, Zuker, N., primary, Chartrand, G., primary, Melland-Smith, M., primary, McLean, C., primary, Fortin, M., primary, Keshavjee, S., primary, Deaninck, F., primary, Cloutier, Z., primary, Shiroky, J., primary, Jarrar, A., primary, Lin, W., primary, Connell, M., primary, Vergis, A., additional, Unger, B., additional, Park, J., additional, Gillman, L., additional, Pace, D., additional, Lam-Tin-Cheung, K., additional, Chadi, S., additional, Quereshy, F., additional, Catton, J., additional, Rubin, B., additional, Bell, J., additional, Marangos, J., additional, Heesters, A., additional, Stuart-McEwan, T., additional, Wright, F., additional, Ahmed, N., additional, Nadler, A., additional, Hallet, J., additional, Chen, L., additional, Hwang, H., additional, Hirpara, D., additional, Sidhu, R., additional, Scott, T., additional, Karimuddin, A., additional, Nguyen, A., additional, Osborn, J., additional, Wiseman, S., additional, Nabata, K., additional, Baker, L., additional, Park, L., additional, Vered, M., additional, Zahrai, A., additional, Shorr, R., additional, Davis, A., additional, McIsaac, D., additional, Tinmouth, A., additional, Fergusson, D., additional, Martel, G., additional, Rummel, S., additional, Stefic-Cubic, M., additional, Stewart, M., additional, Melck, A., additional, Anpalagan, T., additional, Ichhpuniani, S., additional, Lee, Y., additional, Ramji, K., additional, Eskicioglu, C., additional, Deng, S., additional, Greene, B., additional, Tsang, M., additional, Palter, V., additional, Jayaraman, S., additional, Mann, A., additional, Tittley, J., additional, Cadeddu, M., additional, Madani, A., additional, Pasternak, J., additional, Hong, D., additional, Istl, A., additional, Tang, E., additional, Gray, D., additional, Coburn, N., additional, Callum, J., additional, McLeod, R., additional, Pearsall, E., additional, Lin, Y., additional, Turgeon, A., additional, Mahar, A., additional, Kriviraltcheva-Kaneva, P., additional, Lee, L., additional, Cools-Lartigue, J., additional, Ferri, L., additional, Mueller, C., additional, Haas, B., additional, Tillman, B., additional, Guttman, M., additional, Chesney, T., additional, Zuk, V., additional, Hsu, A., additional, Chan, W., additional, Vasdev, R., additional, Huynh, C., additional, Ling, L. Cadili J., additional, Warburton, R., additional, Hameed, M., additional, Williamson, H., additional, Murphy, P., additional, Leslie, K., additional, Hawel, J., additional, Zablotny, S., additional, Roldan, H., additional, Jiang, X., additional, Zheng, B., additional, Fiore, J., additional, Feldman, L., additional, Fried, G., additional, Valanci, S., additional, Cipolla, J., additional, Kaneva, P., additional, Demyttenaere, S., additional, Boutros, M., additional, Alhashemi, M., additional, Purich, K., additional, Verhoeff, K., additional, Shapiro, J., additional, Bigam, D., additional, Kung, J., additional, Mosko, J., additional, Hamilton, P., additional, Ghosh, S., additional, Widder, S., additional, Schiller, D., additional, El Kefraoui, C., additional, Pook, M., additional, Barone, N., additional, Balvardi, S., additional, Montgomery, H., additional, Nguyen-Powanda, P., additional, Rajabiyazdi, F., additional, Elhaj, H., additional, Lapointe-Gagner, M., additional, Olleik, G., additional, Antoun, A., additional, Safa, N., additional, Di Lena, E., additional, Meterissian, S., additional, Meguerditchian, A., additional, Lee, F., additional, Baldini, G., additional, Parpia, S., additional, Ruo, L., additional, Tywonek, K., additional, Lee, S., additional, O’Neill, C., additional, Faisal, N., additional, Alfayyadh, A., additional, Gundayao, M., additional, Meyers, B.M., additional, Habashi, R., additional, McKechnie, T., additional, Levin, M., additional, Aldrich, K., additional, Grantcharov, T., additional, Langerman, A., additional, Anantha, R., additional, Fawcett, V., additional, Hetherington, A., additional, Gervais, M., additional, Rakovich, G., additional, Hu, R., additional, Musselman, R., additional, Raiche, I., additional, Moloo, H., additional, Elnahas, A., additional, Alkhamesi, N., additional, Alnumay, A., additional, Schlachta, C., additional, Zhang, C., additional, Cristancho, S., additional, Ott, M., additional, Niu, B., additional, Balaa, F., additional, Gawad, N., additional, Qiu, Y., additional, Hamann, K., additional, How, N., additional, Leveille, C., additional, Davidson, A., additional, Eqbal, A., additional, Sardiwalla, Y., additional, Korostensky, M., additional, Lee, E., additional, Yang, I., additional, Ren, K., additional, Stukel, T., additional, de Mestral, C., additional, Nathens, A., additional, Karanicolas, P., additional, Lemieux, S., additional, Breton, D., additional, Bouchard, P., additional, Bouchard, A., additional, Grégoire, R., additional, Letarte, F., additional, Bouchard, G., additional, Drolet, S., additional, Avoine, S., additional, Gagné, J., additional, Thibault, C., additional, Jutras Bouthillette, N., additional, Gosselin, M., additional, Stuleanu, T., additional, Jarrar, A., additional, Kolozsvari, N., additional, Nenshi, R., additional, Jerath, A., additional, Gomez, D., additional, Amir, T., additional, Liu, E., additional, Farquharson, S., additional, Mao, R., additional, Lan, L., additional, Yan, J., additional, Allard-Coutu, A., additional, Tin, R., additional, Brisebois, R., additional, Bradley, N., additional, Walser, E., additional, Hartford, L., additional, Van Koughnett, J., additional, Vogt, K., additional, Hilsden, R., additional, Parry, N., additional, Allen, L., additional, Jones, J., additional, Neumann, K., additional, Strickland, M., additional, O’Dochartaigh, D., additional, Lobay, K., additional, Kabaroff, A., additional, Chang, E., additional, Beck, J., additional, Davidson, J., additional, Jones, S., additional, Van Hooren, T., additional, El Hafid, M., additional, Dang, J., additional, Mocanu, V., additional, Lutzak, G., additional, Sultanian, R., additional, Wong, C., additional, Karmali, S., additional, Petrera, M., additional, Pickell, M., additional, Auer, R., additional, Li, B., additional, Sun, W., additional, Jogiat, U., additional, Switzer, N., additional, Al Hinai, A., additional, Cieply, A., additional, Hawes, H., additional, Joos, E., additional, Saleh, A., additional, Engels, P., additional, Kwong, M., additional, Ellsmere, J., additional, Chang, D., additional, Hutter, M., additional, Spence, R., additional, Vasilevsky, C., additional, Morin, N., additional, Longtin, Y., additional, Liberman, S., additional, Montpetit, P., additional, Poirier, M., additional, Mukherjee, K., additional, Sebajang, H., additional, Younan, R., additional, Schwenter, F., additional, De Broux, E., additional, Skelhorne-Gross, G., additional, Beckett, A., additional, Nantais, J., additional, Kay, J., additional, Lohre, R., additional, Ayeni, O., additional, Goel, D., additional, de SA, D., additional, Hylton, D., additional, Bedard, E., additional, Johnson, S., additional, Laing, B., additional, Valji, A., additional, Hanna, W., additional, Turner, S., additional, Akhtar-Danesh, N., additional, Shargall, Y., additional, Gupta, V., additional, Kidane, B., additional, Limbachia, J., additional, Farrokhyar, F., additional, Leontiadis, G., additional, Patel, Y., additional, Churchill, I., additional, Xie, F., additional, Seely, A., additional, Spicer, J., additional, Yasufuku, K., additional, Sullivan, K., additional, Beauchamp, M., additional, Wald, J., additional, Mbuagbaw, L., additional, Agzarian, J., additional, Finley, C., additional, Fahim, C., additional, Olaiya, O., additional, Begum, H., additional, Palma, D., additional, Warner, A., additional, Malthaner, R., additional, Fortin, D., additional, Qiabi, M., additional, Nayak, R., additional, Nguyen, T., additional, Louie, A., additional, Rodrigues, G., additional, Yaremko, B., additional, Laba, J., additional, Inculet, R., additional, Mador, B., additional, Lai, H., additional, White, J., additional, Kim, M., additional, Darling, G., additional, Rousseau, M., additional, Samarasinghe, Y., additional, Lee, M., additional, Thiru, L., additional, Levine, O., additional, Juergens, R., additional, Brogly, S., additional, Li, W., additional, Lougheed, D., additional, Petsikas, D., additional, Gatti, A., additional, Anestee, C., additional, Gilbert, S., additional, Sundaresan, S., additional, Villeneuve, P., additional, Maziak, D., additional, Ashrafi, A., additional, Tregobov, N., additional, Hassanzadeh, N., additional, Stone, S., additional, Panjwani, A., additional, Bong, T., additional, Bond, R., additional, Hafizi, A., additional, Rayes, R., additional, Milette, S., additional, Vagai, M., additional, Usatii, M., additional, Chandrasekaran, A., additional, Giannias, B., additional, Bourdeau, F., additional, Sangwan, V., additional, Bertos, N., additional, Moraes, C., additional, Huang, S., additional, Quail, D., additional, Walsh, L., additional, Camilleri-Broet, S., additional, Fiset, P., additional, Bilgic, E., additional, Quaiattini, A., additional, Maurice-Ventouris, M., additional, Najmeh, S., additional, Lu, J., additional, Malhan, R., additional, Brennan, K., additional, French, D., additional, Momtazi, M., additional, Solaja, O., additional, Donahoe, L., additional, Bedard, P., additional, Hansen, A., additional, De Perrot, M., additional, Simone, A., additional, Huang, J., additional, Murthy, S., additional, Lin, J., additional, Li, H., additional, Crowther, M., additional, Linkins, L., additional, Lau, E., additional, Schneider, L., additional, Douketis, J., additional, Allen-Avodabo, C., additional, Davis, L., additional, Zhao, H., additional, Sirois, C., additional, Mulder, D., additional, Aftab Abdul, S., additional, Nguyen, D., additional, Anstee, C., additional, Delic, E., additional, Sasewich, H., additional, Islam, T., additional, Low, D., additional, Al Rawahi, A., additional, Kay, M., additional, Shayegan, B., additional, Adili, A., additional, Chouiali, F., additional, Muthukrishnan, N., additional, Maleki, F., additional, Ovens, K., additional, Gold, M., additional, Sorin, M., additional, Falutz, R., additional, Forghani, R., additional, Kennedy, R., additional, Bigsby, R., additional, Bharadwaj, S., additional, Gowing, S., additional, Pearce, K., additional, Kumar, S., additional, Gingrich, M., additional, Ahmadzai, Z., additional, Thavorn, K., additional, Namavarian, A., additional, Mohammed, A., additional, Uddin, S., additional, Jones, D., additional, Behzadi, A., additional, Brar, A., additional, Buduhan, G., additional, Tan, L., additional, Liu, R., additional, Srinathan, S., additional, Levy, J., additional, Ringash, J., additional, Sutradhar, R., additional, Bednarek, L., additional, MacDonald, D., additional, Enns, S., additional, Tan, A., additional, Poole, E., additional, Pascoe, C., additional, Karakach, T., additional, Halayko, A., additional, Fang, B., additional, Birch, D., additional, Singh, H., additional, Hershorn, O., additional, Hochman, D., additional, Helewa, R., additional, Robertson, R., additional, Lipson, M., additional, Afzal, A., additional, Maclean, A., additional, Roen, S., additional, Buie, W., additional, Chu, M., additional, Amin, N., 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additional, Malhotra, A., additional, Graham, C., additional, MacLean, A., additional, Beck, P., additional, Jijon, H., additional, Ferraz, J., additional, Kong, W., additional, Gyawali, B., additional, Hanna, T., additional, Chung, W., additional, Nanji, S., additional, Booth, C., additional, Awan, A., additional, Serrano, P., additional, Chanco, M., additional, Wen, V., additional, Singh, N., additional, Peiris, L., additional, Pasieka, J., additional, Ghatage, P., additional, Buie, D., additional, Bouchard-Fortier, A., additional, Mack, L., additional, Zheng, W., additional, Swallow, C., additional, Reedijk, M., additional, Prus-Czrnecka, Z., additional, Delmar, L., additional, Villiard, R., additional, Martel, É., additional, Cadrin-Chênevert, A., additional, Ledoux, É., additional, Racicot, C., additional, Bazzarelli, A., additional, Pao, J., additional, Zhang, M., additional, McKevitt, E., additional, Kuusk, U., additional, Van Laeken, N., additional, Bovill, E., additional, Isaac, K., additional, Dingee, C., additional, Cuthbert, C., additional, Fergus, K., additional, Barbera, L., additional, Efegoma, Y., additional, Howell, D., additional, Isherwood, S., additional, Levasseur, N., additional, Scheer, A., additional, Simmons, C., additional, Srikantham, A., additional, Temple-Orberle, C., additional, Xu, Y., additional, Metcalfe, K., additional, Quan, M., additional, la, J., additional, Merchant, S., additional, Digby, G., additional, Brind’Amour, A., additional, Sidéris, L., additional, Dubé, P., additional, De Guerke, L., additional, Fortin, S., additional, Auclair, M., additional, Trilling, B., additional, Tremblay, J., additional, Hopkins), B., additional, Wong, S., additional, Hopkins, B., additional, Dumitra, S., additional, Bazarelli, A., additional, DeGirolamo, K., additional, Ali, A., additional, Eymae, D., additional, Lee, K., additional, Brar, S., additional, Conner, J., additional, Magalhaes, M., additional, Baliski, C., additional, Sari, A., additional, Messenger, D., additional, Driman, D., additional, Assarzadegan, N., additional, Juda, A., additional, Brar, M., additional, Kirsch, R., additional, Singh, K., additional, Lamontagne, A., additional, Gamache, Y., additional, Lee, C., additional, Duckworth, R., additional, Brindle, M., additional, Fraulin, F., additional, Austen, L., additional, Kortbeek, J., additional, Hyndman, M., additional, Jamjoum, G., additional, Yuan Xu, Y., additional, Kong, S., additional, Retrouvey, H., additional, Kerrebijn, I., additional, Butler, K., additional, O’Neill, A., additional, Cil, T., additional, Zhong, T., additional, Hofer, S., additional, McCready, D., additional, Look Hong, N., additional, Skipworth, J., additional, Mah, A., additional, Desai, S., additional, Chung, S., additional, Scudamore, C., additional, Segedi, M., additional, Vasilyeva, E., additional, Li, J., additional, Kim, P., additional, Deprato, A., additional, Dajani, K., additional, Gilbert, R., additional, Smoot, R., additional, Tzeng, C., additional, Rocha, F., additional, Yohanathan, L., additional, Cleary, S., additional, Bertens, K., additional, Badrudin, D., additional, Gala-Lopez, B., additional, Wei, X., additional, Kaliwal, Y., additional, Wei, A., additional, Barrette, B., additional, Pelletier, S., additional, Thebault, P., additional, Beaudry-Simoneau, E., additional, Rong, Z., additional, Plasse, M., additional, Dagenais, A. Roy M., additional, Létourneau, R., additional, Lapointe, R., additional, Vandenbroucke-Menu, F., additional, Nguyen, B., additional, Soucy, G., additional, Turcotte, S., additional, Waugh, E., additional, Quan, D., additional, Skaro, A., additional, Glinka, J., additional, Jada, G., additional, Daza, J., additional, Li, V., additional, Msallak, H., additional, Zhang, B., additional, Workneh, A., additional, Faisal, S., additional, Faisal, R., additional, Fabbro, M., additional, Gu, C., additional, Claassen, M., additional, Sapisochin, G., additional, Lemke, M., additional, Breadner, D., additional, Welch, S., additional, Lester, E., additional, Shapiro, A., additional, Eurich, D., additional, Nayyar, A., additional, Suraju, M., additional, Williams-Perez, S., additional, Ear, P., additional, Chan, C., additional, Rivers-Bowerman, M., additional, Costa, A., additional, Stueck, A., additional, Campbell, N., additional, Allen, S., additional, Lenet, T., additional, Golding, H., additional, McKeown, S., additional, Flemming, J., additional, Groome, P., additional, Djerboua, M., additional, Girard, E., additional, Morency-Potvin, P., additional, Dagenais, M., additional, Roy, A., additional, Letourneau, R., additional, Simoneau, E., additional, Oakley, M., additional, Misheva, B., additional, Bendavid, Y., additional, Smith, L., additional, Tan, J., additional, Kahn, U., additional, Paré, X., additional, Doyon, A., additional, Schwenger, K., additional, Yadav, J., additional, Fischer, S., additional, Jackson, T., additional, Allard, J., additional, Okrainec, A., additional, Anvari, S., additional, Lovrics, O., additional, Aditya, I., additional, Khondker, A., additional, Walsh, M., additional, Hardy, K., additional, Romanescu, R., additional, Linton, J., additional, Fowler-Woods, M., additional, Fowler-Woods, A., additional, Shingoose, G., additional, Zmudzinski, M., additional, Archer, V., additional, Abu Halimah, J., additional, Boudreau, V., additional, Marcil, G., additional, Mierzwa, A., additional, Hardy-Henry, A., additional, and Hagen, J., additional

Published
2021
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10. 1307P Blood-based genomic profiling of advanced non-small cell lung cancer (aNSCLC) patients (pts) from blood first assay screening trial (BFAST) and comparison with real-world data (RWD)

Author

Dziadziuszko, R., primary, Zhang, Q., additional, Li, X., additional, Paul, S.M., additional, Sugidono, M., additional, Mocci, S., additional, Kinkolykh, A., additional, Shames, D.S., additional, Archer, V., additional, Mathisen, M.S., additional, Jin, D.X., additional, Gadgeel, S.M., additional, Peters, S., additional, and Mok, T., additional

Published
2020
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14. IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC

Author

Cappuzzo, F., primary, McCleod, M., additional, Hussein, M., additional, Morabito, A., additional, Rittmeyer, A., additional, Conter, H.J., additional, Kopp, H.-G., additional, Daniel, D., additional, McCune, S., additional, Mekhail, T., additional, Zer, A., additional, Reinmuth, N., additional, Sadiq, A., additional, Archer, V., additional, Ochi Lohmann, T., additional, Wang, L., additional, Kowanetz, M., additional, Lin, W., additional, Sandler, A., additional, and West, H., additional

Published
2018
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16. LBA53 - IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC

Author

Cappuzzo, F., McCleod, M., Hussein, M., Morabito, A., Rittmeyer, A., Conter, H.J., Kopp, H.-G., Daniel, D., McCune, S., Mekhail, T., Zer, A., Reinmuth, N., Sadiq, A., Archer, V., Ochi Lohmann, T., Wang, L., Kowanetz, M., Lin, W., Sandler, A., and West, H.

Published
2018
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17. A randomized controlled trial of a smoking cessation intervention conducted among prisoners

Author

Richmond, R., Indig, D., Butler, Tony, Wilhelm, K., Archer, V., Wodak, A., Richmond, R., Indig, D., Butler, Tony, Wilhelm, K., Archer, V., and Wodak, A.

Abstract

Aim: To evaluate the efficacy of nortriptyline (NOR) added to a multi-component smoking cessation intervention, which included cognitive-behavioural therapy (CBT) and provision of nicotine replacement therapy (NRT). Design: Randomized controlled trial (RCT) comparing two study groups with blinded follow-up at 3, 6 and 12 months. Both groups received a multi-component smoking cessation intervention comprising two half-hour individual sessions of CBT and NRT with either active NOR or placebo. Setting: Prisons in New South Wales (17) and Queensland (one), Australia. Participants: A total of 425 male prisoners met inclusion criteria and were allocated to either treatment (n=206) or control group (n=219). Measurements: Primary end-points at 3, 6 and 12 months were continuous abstinence, point prevalence abstinence and reporting a 50% reduction in smoking. Smoking status was confirmed by expired carbon monoxide, using a cut-point of =10 parts per million. Findings: Participants' demographics and baseline tobacco use were similar in treatment and control groups. Based on an intention-to-treat analysis, continuous abstinence between the treatment and control groups was not significantly different at 3 months (23.8 versus 16.4%), 6 months (17.5 versus 12.3%) and 12 months (11.7 versus 11.9%). Conclusion: Adding nortriptyline to a smoking cessation treatment package consisting of behavioural support and nicotine replacement therapy does not appear to improve long-term abstinence rates in male prisoners. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Published
2013

18. Heroin use impairs smoking cessation among Australian prisoners

Author

Indig, D., Wodak, A., Richmond, R., Butler, Tony, Archer, V., Wilhelm, K., Indig, D., Wodak, A., Richmond, R., Butler, Tony, Archer, V., and Wilhelm, K.

Abstract

Background: Prisoners have extremely high rates of smoking with rates 3-4 times higher than the general community. Many prisoners have used heroin. The aims of this study were to investigate the impact of heroin use on smoking cessation and the social determinants of health among prisoners. Methods. Secondary analysis of data from a randomised controlled trial of a multi-component smoking cessation intervention involving 425 Australian male prisoners. Inmates who, prior to imprisonment, used heroin regularly were compared to those who did not use heroin regularly. Self-reported smoking status was validated at baseline and each follow-up by measuring carbon monoxide levels. Readings exceeding 10 ppm were defined as indicating current smoking. Results: Over half (56.5%) of the participants had ever used heroin while 37.7% regularly (daily or almost daily) used heroin in the year prior to entering prison. Prisoners who regularly used heroin had significantly worse social determinants of health and smoking behaviours, including lower educational attainment, more frequent incarceration and earlier initiation into smoking. Prisoners who regularly used heroin also used and injected other drugs significantly more frequently. At 12-month follow-up, the smoking cessation of prisoners who had regularly used heroin was also significantly lower than prisoners who did not regularly use heroin, a finding confirmed by logistic regression. Conclusions: Regular heroin use prior to imprisonment is an important risk factor for unsuccessful attempts to quit smoking among prisoners and is also associated with worse social determinants of health, higher drug use, and worse smoking behaviours. More effective and earlier smoking cessation interventions are required for particularly disadvantaged groups. Trial registration. This trial is registered with the Australian New Zealand Clinical Trials Registry 12606000229572. © 2013 Indig et al.; licensee BioMed Central Ltd.

Published
2013

19. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects

Author

Lebrun-Vignes, B, Archer, V Corbrion, Diquet, B, Levron, J C, Chosidow, O, Puech, A J, and Warot, D

Subjects
Adult, Male, Bodily Secretions, Antifungal Agents, Cross-Over Studies, Hydrocortisone, Prednisolone, Humans, Drug Interactions, Itraconazole, Glucocorticoids, Methylprednisolone
Abstract

Itraconazole is a potent inhibitor of CYP3A4 activity and is often used in combination with corticosteroids. Since the latter are partly metabolized by CYP3A4, we studied the interaction between itraconazole, prednisone and methylprednisolone in healthy male subjects.The effects of 4 days administration of oral itraconazole (400 mg on the first day then 200 mg day-1 for 3 days) on the pharmacokinetics of prednisolone after a single oral dose of prednisone (60 mg) and the pharmacokinetics of methylprednisolone after single oral dose of methylprednisolone (48 mg) were studied in 14 healthy male subjects in a two-period cross-over trial. Plasma cortisol concentrations were determined as a pharmacodynamic index.Itraconazole increased the mean area under the methylprednisolone concentration-time curve from 2773 ng ml-1 h to 7011 ng ml-1 h (P0.001) and the elimination half-life from 3.2 h to 5.5 h (P0.001). The pharmacokinetics of prednisolone were unchanged. Cortisol concentrations at 24 h were lower after administration of methylprednisolone with itraconazole than after methylprednisolone alone (24 ng ml-1 vs 109 ng ml-1, P0.001).Itraconazole increased methylprednisolone concentrations markedly with enhanced suppression of endogenous cortisol secretion, but had no effect on prednisolone pharmacokinetics. The pharmacokinetic interaction between methylprednisolone and itraconazole is probably related to inhibition of hepatic CYP3A4 activity by itraconazole.

Published
2001

20. The challenges of reducing tobacco use among prisoners

Author

Richmond, R., Butler, Tony, Indig, D., Wilhelm, K., Archer, V., Wodak, A., Richmond, R., Butler, Tony, Indig, D., Wilhelm, K., Archer, V., and Wodak, A.

Abstract

Issue. The prevalence of smoking among prisoners is exceptionally high and is often comorbid with alcohol and drug problems, mental illness and other health problems. This review paper summarises the literature and available research related to smoking prevalence and smoking cessation initiatives among prisoners and identifies areas of need for further research and intervention. Approach. This paper highlights three studies conducted in the New South Wales prison system which attempt to address these high rates of smoking including a feasibility study, a focus group study and a randomised controlled trial. Key Findings. The challenges of making systems-level changes to address these high rates of smoking are discussed including a recent National Summit on Tobacco Smoking in Prisons. Implications. Dissemination of research findings has assisted in highlighting the importance of tobacco smoking among prisoners and the need to develop culturally and setting appropriate smoking cessation initiatives for prisoners. Conclusions. As one of the most marginalised and socially disadvantaged populations in Australia, prisoners represent an important population to target for smoking cessation programs and interventions. This paper highlights a number of initiatives undertaken to address this problem and suggests directions for the future.[Richmond RL, Butler TG, Indig D, Wilhelm KA, Archer VA, Wodak AD. The challenges of reducing tobacco use among prisoners. Drug Alcohol Rev 2012;31:625-630] © 2012 Australasian Professional Society on Alcohol and other Drugs.

Published
2012

21. Cardiovascular risk among Aboriginal and non-Aboriginal smoking male prisoners: inequalities compared to the wider community

Author

Richmond, RL, Wilhelm, KA, Indig, D, Butler, TG, Archer, V, Wodak, AD, Richmond, RL, Wilhelm, KA, Indig, D, Butler, TG, Archer, V, and Wodak, AD

Abstract

BackgroundCardiovascular risk factors (CVRF) were collected as part of a randomised controlled trial of a multi-component intervention to reduce smoking among male prisoners. Cross-sectional baseline data on CVRF were compared among smoking male prisoners and males of similar age in the general population. Methods425 smoking prisoners were recruited (n = 407 in New South Wales; 18 in Queensland), including 15% of Aboriginal descent (mean age 33 years; median sentence length 3.6 years). We measured CVRF such as smoking, physical activity, blood pressure, risky alcohol use, symptoms of depression, and low socioeconomic status. ResultsWe found that 39% of prisoners had 3+ CVRF, compared to 10% in a general community sample of most disadvantaged men of a similar age. Significantly more Aboriginal prisoners had 3+ CVRF than non-Aboriginal prisoners (55% vs 36%, p

Published
2011

23. Cardiovascular risk among Aboriginal and non-Aboriginal smoking male prisoners: Inequalities compared to the wider community

Author

Richmond, R., Wilhelm, K., Indig, D., Butler, Tony, Archer, V., Wodak, A., Richmond, R., Wilhelm, K., Indig, D., Butler, Tony, Archer, V., and Wodak, A.

Abstract

Background: Cardiovascular risk factors (CVRF) were collected as part of a randomised controlled trial of a multi-component intervention to reduce smoking among male prisoners. Cross-sectional baseline data on CVRF were compared among smoking male prisoners and males of similar age in the general population. Methods. 425 smoking prisoners were recruited (n = 407 in New South Wales; 18 in Queensland), including 15% of Aboriginal descent (mean age 33 years; median sentence length 3.6 years). We measured CVRF such as smoking, physical activity, blood pressure, risky alcohol use, symptoms of depression, and low socioeconomic status. Results: We found that 39% of prisoners had 3+ CVRF, compared to 10% in a general community sample of most disadvantaged men of a similar age. Significantly more Aboriginal prisoners had 3+ CVRF than non-Aboriginal prisoners (55% vs 36%, p < 0.01) and were twice as likely to have 4+ CVRF (27% vs 12%). In addition to all prisoners in this study being a current smoker (with 70% smoking 20+ cigarettes per day), the prevalence of other CVRF was very high: insufficient physical activity (23%); hypertension (4%), risky drinking (52%), symptoms of depression (14%) and low socioeconomic status (SES) (44%). Aboriginal prisoners had higher levels of risky alcohol use, symptoms of depression, and were more likely to be of low SES. Conclusion: Prisoners are at high risk for developing cardiovascular disease compared to even the most disadvantaged in their community and should be the focus of specific public health interventions. Trial Registration. This trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN#12606000229572. © 2011 Richmond et al; licensee BioMed Central Ltd.

Published
2011

25. Chromosomal translocations and leukaemia: a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis

Author

Terence Rabbitts, Axelson H, Forster A, Grutz G, Lavenir I, Larson R, Osada H, Valge-Archer V, Wadman I, and Warren A

Subjects
Transcription, Genetic, Chromosomes, Human, Pair 11, Mice, Transgenic, LIM Domain Proteins, Translocation, Genetic, Hematopoiesis, DNA-Binding Proteins, Mice, Proto-Oncogene Proteins, Metalloproteins, Proto-Oncogenes, Animals, Humans, Leukemia-Lymphoma, Adult T-Cell, Erythropoiesis, Adaptor Proteins, Signal Transducing
Abstract

The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development.

Published
1997

31. Lung cancer risks of underground miners: cohort and case-control studies

Author

Archer, V. E.

Subjects
Cohort Studies, Occupational Diseases, Cocarcinogenesis, Lung Neoplasms, Neoplasms, Radiation-Induced, Radon, Risk Factors, Smoking, Humans, Mining, Research Article
Abstract

All underground mines have higher radon levels than are found in surface air. Ventilation is the primary method of controlling radon levels. Fourteen cohort and seven case-control studies done on underground miners are reviewed; they include many types of ore. Only five of the studies deal with more than 100 lung cancer deaths. Variations in the attributable risk are given. Some generalizations can be drawn from these studies: the longer the follow-up, the greater is the attributable risk, even though the relative risk is reasonably constant. The induction-latent period is quite variable but is shortened by high exposure rates, by cigarette smoking, and by increasing age at start of mining. The predominant histological type of lung cancer among miners changed from small-cell undifferentiated for short follow-up time to epidermoid after long follow-up times. With short follow-up time, a multiplicative interaction between smoking and radiation was indicated, but, with long follow-up time, the two factors appear to be simply additive. This difference is probably due to the shortened latent period among cigarette smokers, not to synergism.

Published
1988

38. Cardiovascular risk among Aboriginal and non-Aboriginal smoking male prisoners: inequalities compared to the wider community

Author

Indig Devon, Wilhelm Kay A, Richmond Robyn L, Butler Tony G, Archer Vicki A, and Wodak Alex D

Subjects
Public aspects of medicine, RA1-1270
Abstract

Abstract Background Cardiovascular risk factors (CVRF) were collected as part of a randomised controlled trial of a multi-component intervention to reduce smoking among male prisoners. Cross-sectional baseline data on CVRF were compared among smoking male prisoners and males of similar age in the general population. Methods 425 smoking prisoners were recruited (n = 407 in New South Wales; 18 in Queensland), including 15% of Aboriginal descent (mean age 33 years; median sentence length 3.6 years). We measured CVRF such as smoking, physical activity, blood pressure, risky alcohol use, symptoms of depression, and low socioeconomic status. Results We found that 39% of prisoners had 3+ CVRF, compared to 10% in a general community sample of most disadvantaged men of a similar age. Significantly more Aboriginal prisoners had 3+ CVRF than non-Aboriginal prisoners (55% vs 36%, p < 0.01) and were twice as likely to have 4+ CVRF (27% vs 12%). In addition to all prisoners in this study being a current smoker (with 70% smoking 20+ cigarettes per day), the prevalence of other CVRF was very high: insufficient physical activity (23%); hypertension (4%), risky drinking (52%), symptoms of depression (14%) and low socioeconomic status (SES) (44%). Aboriginal prisoners had higher levels of risky alcohol use, symptoms of depression, and were more likely to be of low SES. Conclusion Prisoners are at high risk for developing cardiovascular disease compared to even the most disadvantaged in their community and should be the focus of specific public health interventions. Trial Registration This trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN#12606000229572.

Published
2011
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40. CHROMOSOMAL TRANSLOCATIONS AND LEUKAEMIA: A ROLE FOR LMO2 IN T CELL ACUTE LEUKAEMIA, IN TRANSCRIPTION AND IN ERYTHROPOIESIS.

Author

RABBITTS, T. H., AXELSON, H., FORSTER, A., GRUTZ, G., LAVENIR, I., LARSON, R., OSADA, H., VALGE-ARCHER, V., WADMAN, I., and WARREN, A.

Subjects
CHROMOSOMAL translocation, ONCOGENES, ADULT T-cell leukemia, T-cell receptor genes, PROTEINS, TUMOR growth, TUMOR genetics
Abstract

The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development. [ABSTRACT FROM AUTHOR]

Published
1997

42. Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial.

Author

Peters S, Gadgeel SM, Mok T, Nadal E, Kilickap S, Swalduz A, Cadranel J, Sugawara S, Chiu CH, Yu CJ, Moskovitz M, Tanaka T, Nersesian R, Shagan SM, Maclennan M, Mathisen M, Bhagawati-Prasad V, Diarra C, Assaf ZJ, Archer V, and Dziadziuszko R

Subjects
Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Liquid Biopsy, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Indazoles therapeutic use, Indazoles adverse effects, Benzamides therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases genetics
Abstract

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 ., (© 2024. The Author(s).)

Published
2024
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43. Alectinib Versus Crizotinib in Asian Patients With Treatment-Naïve Advanced ALK -Positive NSCLC: Five-Year Update From the Phase 3 ALESIA Study.

Author

Zhou C, Lu Y, Kim SW, Reungwetwattana T, Zhou J, Zhang Y, He J, Yang JJ, Cheng Y, Lee SH, Chang J, Fang J, Liu Z, Bu L, Qian L, Xu T, Archer V, Hilton M, Zhou M, and Zhang L

Abstract

Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced ALK -positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the "last patient in" date., Methods: Adult patients with treatment-naïve, advanced ALK -positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62). The primary endpoint was investigator-assessed progression-free survival. Secondary or exploratory endpoints included overall survival, objective response rate, time to CNS progression, and safety., Results: At the data cutoff (May 16, 2022), the median survival follow-up was 61 and 51 months in the alectinib and crizotinib arms, respectively. Median progression-free survival was 41.6 months with alectinib versus 11.1 months with crizotinib (stratified hazard ratio = 0.33, 95% confidence interval: 0.23-0.49). Overall survival data remain immature; 5-year overall survival rates were 66.4% (alectinib arm) versus 56.1% (crizotinib arm). Objective response rate was 91.2% versus 77.4% with alectinib and crizotinib, respectively. CNS progression was delayed with alectinib versus crizotinib (cause-specific hazard ratio = 0.16, 95% confidence interval: 0.08-0.32). Median treatment duration was longer with alectinib versus crizotinib (42.3 versus 12.6 mo). No new safety signals were observed., Conclusions: With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced ALK -positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced ALK -positive NSCLC., Competing Interests: Prof. Caicun Zhou reports receiving consulting fees from Innovent Biologics, Jiangsu Hengrui Pharmaceuticals, Qilu Pharmaceutical, and TopAlliance Biosciences; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alice Pharma, AnHeart Therapeutics, Amoy Diagnostics, Boehringer Ingelheim, CStone Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche Ltd., Innovent Biologics, Jiangsu Hengrui Pharmaceuticals, Luye Pharma Group, Merck Sharp & Dohme, Qilu Pharmaceutical, Sanofi, and TopAlliance Biosciences. Prof. You Lu reports invited speaker roles for BeiGene, Roche/Genentech, AstraZeneca, Pfizer; advisory roles for Roche/Genentech, AstraZeneca, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme, and BeiGene; and leadership roles for Roche/Genentech, AstraZeneca, and BeiGene. Dr. Sang-We Kim reports invited speaker roles for Amgen, Boehringer Ingelheim, Janssen, Novartis, and Takeda; receiving research funding from 10.13039/100019265Yuhan; and advisory roles from Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Novartis, Takeda, and Yuhan. Dr. Thanyanan Reungwetwattana reports advisory board roles from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd., Johnson & Johnson, Merck Sharp & Dohme, Novartis, and Yuhan; participation in clinical research for AstraZeneca, Boehringer Ingelheim, F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme, Novartis, and Yuhan; and speaker roles for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme, Novartis, Yuhan, and Zuellig Pharma. Prof. Jianying Zhou, Prof. Yiping Zhang, Prof. Jianxing He, Prof. Jin-Ji.Yang and Prof. Ying Cheng report no conflicts of interest. Prof. Se-Hoon Le reports receiving research funding (institution) from 10.13039/100004325AstraZeneca, 10.13039/100019703Lunit, and 10.13039/100004334Merck; and consulting/advisory roles from AstraZeneca, Bristol-Myers Squibb/Ono Pharmaceuticals, F. Hoffmann-La Roche Ltd., IMBdx, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and Takeda. Prof. Jianhua Chang, Dr. Jian Fang and Prof. Zhe Liu report no conflicts of interest. Ms. Lilian Bu, Dr. Li Qian and Dr. Tingting Xu report employment with F. Hoffmann-La Roche Ltd. Dr. Venice Archer and Ms. Magalie Hilton report employment and stocks/shares with F. Hoffmann-La Roche Ltd. Dr. Mingzhu Zhou reports employment with F. Hoffmann-La Roche Ltd. Prof. Li Zhang reports consulting/advisory roles for AstraZeneca and Innovent Biologics; and receiving research funding (institution) from Akeso Biopharma, AstraZeneca, Bristol-Myers Squibb, Chia Tai Tianqing Pharmaceutical Group, Junshi Biosciences, and Qilu Pharmaceutical., (© 2024 The Authors.)

Published
2024
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44. The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

Author

Hardaker EL, Sanseviero E, Karmokar A, Taylor D, Milo M, Michaloglou C, Hughes A, Mai M, King M, Solanki A, Magiera L, Miragaia R, Kar G, Standifer N, Surace M, Gill S, Peter A, Talbot S, Tohumeken S, Fryer H, Mostafa A, Mulgrew K, Lam C, Hoffmann S, Sutton D, Carnevalli L, Calero-Nieto FJ, Jones GN, Pierce AJ, Wilson Z, Campbell D, Nyoni L, Martins CP, Baker T, Serrano de Almeida G, Ramlaoui Z, Bidar A, Phillips B, Boland J, Iyer S, Barrett JC, Loembé AB, Fuchs SY, Duvvuri U, Lou PJ, Nance MA, Gomez Roca CA, Cadogan E, Critichlow SE, Fawell S, Cobbold M, Dean E, Valge-Archer V, Lau A, Gabrilovich DI, and Barry ST

Subjects
Humans, Animals, Mice, B7-H1 Antigen, Tumor Microenvironment, Cell Line, Tumor, Immunotherapy, Disease Models, Animal, Ataxia Telangiectasia Mutated Proteins, CD8-Positive T-Lymphocytes, Neoplasms, Indoles, Morpholines, Pyrimidines, Sulfonamides
Abstract

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8 + T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8 + T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity., (© 2024. The Author(s).)

Published
2024
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45. 2023 Canadian Surgery Forum: Sept. 20-23, 2023.

Author

Brière R, Émond M, Benhamed A, Blanchard PG, Drolet S, Habashi R, Golbon B, Shellenberger J, Pasternak J, Merchant S, Shellenberger J, La J, Sawhney M, Brogly S, Cadili L, Horkoff M, Ainslie S, Demetrick J, Chai B, Wiseman K, Hwang H, Alhumoud Z, Salem A, Lau R, Aw K, Nessim C, Gawad N, Alibhai K, Towaij C, Doan D, Raîche I, Valji R, Turner S, Balmes PN, Hwang H, Hameed SM, Tan JGK, Wijesuriya R, Tan JGK, Hew NLC, Wijesuriya R, Lund M, Hawel J, Gregor J, Leslie K, Lenet T, McIsaac D, Hallet J, Jerath A, Lalu M, Nicholls S, Presseau J, Tinmouth A, Verret M, Wherrett C, Fergusson D, Martel G, Sharma S, McKechnie T, Talwar G, Patel J, Heimann L, Doumouras A, Hong D, Eskicioglu C, Wang C, Guo M, Huang L, Sun S, Davis N, Wang J, Skulsky S, Sikora L, Raîche I, Son HJ, Gee D, Gomez D, Jung J, Selvam R, Seguin N, Zhang L, Lacaille-Ranger A, Sikora L, McIsaac D, Moloo H, Follett A, Holly, Organ M, Pace D, Balvardi S, Kaneva P, Semsar-Kazerooni K, Mueller C, Vassiliou M, Al Mahroos M, Fiore JF Jr, Schwartzman K, Feldman L, Guo M, Karimuddin A, Liu GP, Crump T, Sutherland J, Hickey K, Bonisteel EM, Umali J, Dogar I, Warden G, Boone D, Mathieson A, Hogan M, Pace D, Seguin N, Moloo H, Li Y, Best G, Leong R, Wiseman S, Alaoui AA, Hajjar R, Wassef E, Metellus DS, Dagbert F, Loungnarath R, Ratelle R, Schwenter F, Debroux É, Wassef R, Gagnon-Konamna M, Pomp A, Richard CS, Sebajang H, Alaoui AA, Hajjar R, Dagbert F, Loungnarath R, Sebajang H, Ratelle R, Schwenter F, Debroux É, Wassef R, Gagnon-Konamna M, Pomp A, Santos MM, Richard CS, Shi G, Leung R, Lim C, Knowles S, Parmar S, Wang C, Debru E, Mohamed F, Anakin M, Lee Y, Samarasinghe Y, Khamar J, Petrisor B, McKechnie T, Eskicioglu C, Yang I, Mughal HN, Bhugio M, Gok MA, Khan UA, Fernandes AR, Spence R, Porter G, Hoogerboord CM, Neumann K, Pillar M, Guo M, Manhas N, Melck A, Kazi T, McKechnie T, Jessani G, Heimann L, Lee Y, Hong D, Eskicioglu C, McKechnie T, Tessier L, Archer V, Park L, Cohen D, Parpia S, Bhandari M, Dionne J, Eskicioglu C, Bolin S, Afford R, Armstrong M, Karimuddin A, Leung R, Shi G, Lim C, Grant A, Van Koughnett JA, Knowles S, Clement E, Lange C, Roshan A, Karimuddin A, Scott T, Nadeau K, Macmillan J, Wilson J, Deschenes M, Nurullah A, Cahill C, Chen VH, Patterson KM, Wiseman SM, Wen B, Bhudial J, Barton A, Lie J, Park CM, Yang L, Gouskova N, Kim DH, Afford R, Bolin S, Morris-Janzen D, McLellan A, Karimuddin A, Archer V, Cloutier Z, Berg A, McKechnie T, Wiercioch W, Eskicioglu C, Labonté J, Bisson P, Bégin A, Cheng-Oviedo SG, Collin Y, Fernandes AR, Hossain I, Ellsmere J, El-Kefraoui C, Do U, Miller A, Kouyoumdjian A, Cui D, Khorasani E, Landry T, Amar-Zifkin A, Lee L, Feldman L, Fiore J, Au TM, Oppenheimer M, Logsetty S, AlShammari R, AlAbri M, Karimuddin A, Brown C, Raval MJ, Phang PT, Bird S, Baig Z, Abu-Omar N, Gill D, Suresh S, Ginther N, Karpinski M, Ghuman A, Malik PRA, Alibhai K, Zabolotniuk T, Raîche I, Gawad N, Mashal S, Boulanger N, Watt L, Razek T, Fata P, Grushka J, Wong EG, Hossain I, Landry M, Mackey S, Fairbridge N, Greene A, Borgoankar M, Kim C, DeCarvalho D, Pace D, Wigen R, Walser E, Davidson J, Dorward M, Muszynski L, Dann C, Seemann N, Lam J, Harding K, Lowik AJ, Guinard C, Wiseman S, Ma O, Mocanu V, Lin A, Karmali S, Bigam D, Harding K, Greaves G, Parker B, Nguyen V, Ahmed A, Yee B, Perren J, Norman M, Grey M, Perini R, Jowhari F, Bak A, Drung J, Allen L, Wiseman D, Moffat B, Lee JKH, McGuire C, Raîche I, Tudorache M, Gawad N, Park LJ, Borges FK, Nenshi R, Jacka M, Heels-Ansdell D, Simunovic M, Bogach J, Serrano PE, Thabane L, Devereaux PJ, Farooq S, Lester E, Kung J, Bradley N, Best G, Ahn S, Zhang L, Prince N, Cheng-Boivin O, Seguin N, Wang H, Quartermain L, Tan S, Shamess J, Simard M, Vigil H, Raîche I, Hanna M, Moloo H, Azam R, Ko G, Zhu M, Raveendran Y, Lam C, Tang J, Bajwa A, Englesakis M, Reel E, Cleland J, Snell L, Lorello G, Cil T, Ahn HS, Dube C, McIsaac D, Smith D, Leclerc A, Shamess J, Rostom A, Calo N, Thavorn K, Moloo H, Laplante S, 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Gilbert S, Sundaresan S, Jones D, Seely AJE, Villeneuve PJ, Maziak DE, Pigeon CA, Frigault J, Drolet S, Roy ÈM, Bujold-Pitre K, Courval V, Tessier L, McKechnie T, Lee Y, Park L, Gangam N, Eskicioglu C, Cloutier Z, McKechnie T (McMaster University), Archer V, Park L, Lee J, Patel A, Hong D, Eskicioglu C, Ichhpuniani S, McKechnie T, Elder G, Chen A, Logie K, Doumouras A, Hong D, Benko R, Eskicioglu C, Castelo M, Paszat L, Hansen B, Scheer A, Faught N, Nguyen L, Baxter N, Sharma S, McKechnie T, Khamar J, Wu K, Eskicioglu C, McKechnie T, Khamar J, Lee Y, Tessier L, Passos E, Doumouras A, Hong D, Eskicioglu C, McKechnie T, Khamar J, Sachdeva A, Lee Y, Hong D, Eskicioglu C, Fei LYN, Caycedo A, Patel S, Popa T, Boudreau L, Grin A, Wang T, Lie J, Karimuddin A, Brown C, Phang T, Raval M, Ghuman A, Candy S, Nanda K, Li C, Snelgrove R, Dykstra M, Kroeker K, Wang H, Roy H, Helewa RM, Johnson G, Singh H, Hyun E, Moffatt D, Vergis A, Balmes P, Phang T, Guo M, Liu J, Roy H, Webber S, Shariff F, Helewa RM, Hochman D, Park J, Johnson G, Hyun E, Robitaille S, Wang A, Maalouf M, Alali N, Elhaj H, Liberman S, Charlebois P, Stein B, Feldman L, Fiore JF Jr, Lee L, Hu R, Lacaille-Ranger A, Ahn S, Tudorache M, Moloo H, Williams L, Raîche I, Musselman R, Lemke M, Allen L, Samarasinghe N, Vogt K, Brackstone M, Zwiep T, Clement E, Lange C, Alam A, Ghuman A, Karimuddin A, Phang T, Raval M, Brown C, Clement E, Liu J, Ghuman A, Karimuddin A, Phang T, Raval M, Brown C, Mughal HN, Gok MA, Khan UA, Mughal HN, Gok MA, Khan UA, Mughal HN, Gok MA, Khan UA, Mughal HN, Gok MA, Khan UA, James N, Zwiep T, Van Koughnett JA, Laczko D, McKechnie T, Yang S, Wu K, Sharma S, Lee Y, Park L, Doumouras A, Hong D, Parpia S, Bhandari M, Eskicioglu C, McKechnie T, Tessier L, Lee S, Kazi T, Sritharan P, Lee Y, Doumouras A, Hong D, Eskicioglu C, McKechnie T, Lee Y, Hong D, Dionne J, Doumouras A, Parpia S, Bhandari M, Eskicioglu C, Hershorn O, Ghuman A, Karimuddin A, Brown C, Raval M, Phang PT, Chen A, Boutros M, Caminsky N, Dumitra T, Faris-Sabboobeh S, Demian M, Rigas G, Monton O, Smith A, Moon J, Demian M, Garfinkle R, Vasilevsky CA, Rajabiyazdi F, Boutros M, Courage E, LeBlanc D, Benesch M, Hickey K, Hartwig K, Armstrong C, Engelbrecht R, Fagan M, Borgaonkar M, Pace D, Shanahan J, Moon J, Salama E, Wang A, Arsenault M, Leon N, Loiselle C, Rajabiyazdi F, Boutros M, Brennan K, Rai M, Farooq A, McClintock C, Kong W, Patel S, Boukhili N, Caminsky N, Faris-Sabboobeh S, Demian M, Boutros M, Paradis T, Robitaille S, Dumitra T, Liberman AS, Charlebois P, Stein B, Fiore JF Jr, Feldman LS, Lee L, Zwiep T, Abner D, Alam T, Beyer E, Evans M, Hill M, Johnston D, Lohnes K, Menard S, Pitcher N, Sair K, Smith B, Yarjau B, LeBlanc K, Samarasinghe N, Karimuddin AA, Brown CJ, Phang PT, Raval MJ, MacDonell K, Ghuman A, Harvey A, Phang PT, Karimuddin A, Brown CJ, Raval MJ, Ghuman A, Hershorn O, Ghuman A, Karimuddin A, Raval M, Phang PT, Brown C, Logie K, Mckechnie T, Lee Y, Hong D, Eskicioglu C, Matta M, Baker L, Hopkins J, Rochon R, Buie D, MacLean A, Ghuman A, Park J, Karimuddin AA, Phang PT, Raval MJ, Brown CJ, Farooq A, Ghuman A, Patel S, Macdonald H, Karimuddin A, Raval M, Phang PT, Brown C, Wiseman V, Brennan K, Patel S, Farooq A, Merchant S, Kong W, McClintock C, Booth C, Hann T, Ricci A, Patel S, Brennan K, Wiseman V, McClintock C, Kong W, Farooq A, Kakkar R, Hershorn O, Raval M, Phang PT, Karimuddin A, Ghuman A, Brown C, Wiseman V, Farooq A, Patel S, Hajjar R, Gonzalez E, Fragoso G, Oliero M, Alaoui AA, Rendos HV, Djediai S, Cuisiniere T, Laplante P, Gerkins C, Ajayi AS, Diop K, Taleb N, Thérien S, Schampaert F, Alratrout H, Dagbert F, Loungnarath R, Sebajang H, Schwenter F, Wassef R, Ratelle R, Debroux É, Cailhier JF, Routy B, Annabi B, Brereton NJB, Richard C, Santos MM, Gimon T, MacRae H, de Buck van Overstraeten A, Brar M, Chadi S, Kennedy E, Baker L, Hopkins J, Rochon R, Buie D, MacLean A, Park LJ, Archer V, McKechnie T, Lee Y, McIsaac D, Rashanov P, Eskicioglu C, Moloo H, Devereaux PJ, Alsayari R, McKechnie T, Ichhpuniani S, Lee Y, Eskicioglu C, Hajjar R, Oliero M, Fragoso G, Ajayi AS, Alaoui AA, Rendos HV, Calvé A, Cuisinière T, Gerkins C, Thérien S, Taleb N, Dagbert F, Sebajang H, Loungnarath R, Schwenter F, Ratelle R, Wassef R, Debroux E, Richard C, Santos MM, Kennedy E, Simunovic M, Schmocker S, Brown C, MacLean A, Liberman S, Drolet S, Neumann K, Stotland P, Jhaveri K, Kirsch R, Alnajem H, Alibrahim H, Giundi C, Chen A, Rigas G, Munir H, Safar A, Sabboobeh S, Holland J, Boutros M, Kennedy E, Richard C, Simunovic M, Schmocker S, Brown C, MacLean A, Liberman S, Drolet S, Neumann K, Stotland P, Jhaveri K, Kirsch R, Bruyninx G, Gill D, Alsayari R, McKechnie T, Lee Y, Hong D, Eskicioglu C, Zhang L, Abtahi S, Chhor A, Best G, Raîche I, Musselman R, Williams L, Moloo H, Caminsky NG, Moon JJ, Marinescu D, Pang A, Vasilevsky CA, Boutros M, Al-Abri M, Gee E, Karimuddin A, Phang PT, Brown C, Raval M, Ghuman A, Morena N, Ben-Zvi L, Hayman V, Hou M (University of Calgary), Nguyen D, Rentschler CA, Meguerditchian AN, Mir Z, Fei L, McKeown S, Dinchong R, Cofie N, Dalgarno N, Cheifetz R, Merchant S, Jaffer A, Cullinane C, Feeney G, Jalali A, Merrigan A, Baban C, Buckley J, Tormey S, Benesch M, Wu R, Takabe K, Benesch M, O'Brien S, Kazazian K, Abdalaty AH, Brezden C, Burkes R, Chen E, Govindarajan A, Jang R, Kennedy E, Lukovic J, Mesci A, Quereshy F, Swallow C, Chadi S, Habashi R, Pasternak J, Marini W, Zheng W, Murakami K, Ohashi P, Reedijk M, Hu R, Ivankovic V, Han L, Gresham L, Mallick R, Auer R, Ribeiro T, Bondzi-Simpson A, Coburn N, Hallet J, Cil T, Fontebasso A, Lee A, Bernard-Bedard E, Wong B, Li H, Grose E, Brandts-Longtin O, Aw K, Lau R, Abed A, Stevenson J, Sheikh R, Chen R, Johnson-Obaseki S, Nessim C, Hennessey RL, Meneghetti AT, Bildersheim M, Bouchard-Fortier A, Nelson G, Mack L, Ghasemi F, Naeini MM, Parsyan A, Kaur Y, Covelli A, Quereshy F, Elimova E, Panov E, Lukovic J, Brierley J, Burnett B, Swallow C, Eom A, Kirkwood D, Hodgson N, Doumouras A, Bogach J, Whelan T, Levine M, Parvez E, Ng D, Kazazian K, Lee K, Lu YQ, Kim DK, Magalhaes M, Grigor E, Arnaout A, Zhang J, Yee EK, Hallet J, Look Hong NJ, Nguyen L, Coburn N, Wright FC, Gandhi S, Jerzak KJ, Eisen A, Roberts A, Ben Lustig D, Quan ML, Phan T, Bouchard-Fortier A, Cao J, Bayley C, Watanabe A, Yao S, Prisman E, Groot G, Mitmaker E, Walker R, Wu J, Pasternak J, Lai CK, Eskander A, Wasserman J, Mercier F, Roth K, Gill S, Villamil C, Goldstein D, Munro V, Pathak A (University of Manitoba), Lee D, Nguyen A, Wiseman S, Rajendran L, Claasen M, Ivanics T, Selzner N, McGilvray I, Cattral M, Ghanekar A, Moulton CA, Reichman T, Shwaartz C, Metser U, Burkes R, Winter E, Gallinger S, Sapisochin G, Glinka J, Waugh E, Leslie K, Skaro A, Tang E, Glinka J, Charbonneau J, Brind'Amour A, Turgeon AF, O'Connor S, Couture T, Wang Y, Yoshino O, Driedger M, Beckman M, Vrochides D, Martinie J, Alabduljabbar A, Aali M, Lightfoot C, Gala-Lopez B, Labelle M, D'Aragon F, Collin 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2023
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46. Health literacy strengths and challenges of people in New South Wales prisons: a cross-sectional survey using the Health Literacy Questionnaire (HLQ).

Author

Gill S, Zeki R, Kaye S, Zingirlis P, Archer V, Lewandowski A, Creighton G, Shaw C, and Bowman J

Subjects
Adult, Male, Female, Humans, Young Adult, Middle Aged, Aged, Aged, 80 and over, New South Wales, Australia, Cross-Sectional Studies, Surveys and Questionnaires, Prisons, Health Literacy
Abstract

Background: Health literacy is an important factor for enabling people to manage their health and live long fulfilling lives. People in prison are frequently from marginalised communities, often out of reach of conventional community based health organisations, and have poorer health outcomes. It is essential to understanding the health literacy profiles of people in prison, and its contribution to the well-established health inequities and outcomes of this population. This study aimed to use a multi-dimensional health literacy measurement tool to describe the strengths and challenges of adults incarcerated in NSW prisons., Methods: A cross-sectional survey was conducted for people in prison across 14 publicly operated metropolitan prisons. Data were collected from 471 participants using the Health Literacy Questionnaire (HLQ). Participant characteristics and health conditions were also collected. Data were analysed using descriptive statistics. Effect sizes (ES) for standardised differences in means were used to describe the magnitude of difference between participant characteristic groups., Results: Participants' median age was 38.0 (range 19 - 91) years. Males comprised 81% of the sample, 21% identified as Aboriginal and/or Torres Strait Islander, and 53% reported a health problem. People in prison had lower scores for all nine HLQ scales when compared to the general Australian population. Small to medium ES were seen for mean differences between most demographic groups. Compared to males, females had lower scores for several of the HLQ scales including 'having sufficient information to manage health' (ES 0.30 [95% Confidence Interval (CI) 0.07, 0.53]), 'ability to actively engage with health care professionals' (ES 0.30 [95% CI 0.06, 0.53]), 'navigating the healthcare system' (ES 0.30 [95% CI 0.06, 0.53]), and, 'ability to find good health information' (ES 0.33 [95% CI 0.10, 0.57]). Differing health literacy scale scores with small to medium ES were found when comparing participants by legal status. Mainly small ES were seen when comparing other participant characteristic groups., Conclusions: This study provides insights into the health literacy strengths and challenges for people in NSW prisons. These findings highlight the important role health literacy could have in addressing health disparities in this vulnerable population and can inform prison health services., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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2023
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47. Real-World Comparative Effectiveness of First-Line Alectinib Versus Crizotinib in Patients With Advanced ALK -Positive NSCLC With or Without Baseline Central Nervous System Metastases.

Author

Zhang Q, Lin JJ, Pal N, Polito L, Trinh H, Hilton M, Smoljanović V, Kurtsikidze N, Archer V, and Krebs MG

Abstract

Introduction: Alectinib was found to have superior efficacy to crizotinib in the phase 3 ALEX study and is a preferred initial treatment for patients with advanced ALK -positive NSCLC. To understand the efficacy of alectinib in U.S. clinical practice, we conducted a retrospective real-world comparative effectiveness analysis of first-line alectinib versus crizotinib., Methods: Adults with advanced ALK -positive NSCLC who received first-line alectinib (from December 11, 2015) or crizotinib (from January 1, 2014) were included from a real-world database. Propensity scores were applied to balance baseline characteristics. Real-world data (RWD), including real-world progression-free survival (rwPFS), real-world overall survival, real-world time to new central nervous system (CNS) metastases, and outcomes in patients with or without baseline CNS metastases were analyzed. The ALEX-like RWD cohort (filtered by ALEX laboratory eligibility criteria) was used to compare real-world comparative effectiveness with ALEX., Results: The RWD cohort comprised 364 patients (141 alectinib; 223 crizotinib); rwPFS (weighted hazard ratio [wHR] = 0.46, 95% confidence interval [CI]: 0.33-0.65) and real-world overall survival (wHR = 0.46, 95% CI: 0.31-0.69) were significantly improved with alectinib versus crizotinib. In patients with baseline brain scans, a substantial rwPFS benefit was found regardless of baseline CNS metastases. Real-world time to new CNS metastases was delayed with alectinib versus crizotinib in patients with (wHR = 0.28, 95% CI: 0.16-0.52) and without (wHR = 0.42, 95% CI: 0.24-0.76) baseline CNS metastases. The ALEX-like RWD cohort comprised 325 patients (120 alectinib; 205 crizotinib); alectinib was found to have similar rwPFS benefits with ALEX., Conclusions: Outcomes were significantly improved with first-line alectinib versus crizotinib in patients with advanced ALK -positive NSCLC in the U.S. real-world setting., (© 2023 The Authors.)

Published
2023
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48. ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Author

Mellone M, Piotrowska K, Venturi G, James L, Bzura A, Lopez MA, James S, Wang C, Ellis MJ, Hanley CJ, Buckingham JF, Cox KL, Hughes G, Valge-Archer V, King EV, Beers SA, Jaquet V, Jones GDD, Savelyeva N, Sayan E, Parsons JL, Durant S, and Thomas GJ

Subjects
Humans, Cell Differentiation, Myofibroblasts metabolism, Drug Resistance, Neoplasm, Ataxia Telangiectasia Mutated Proteins metabolism, Cancer-Associated Fibroblasts metabolism, Immunotherapy, Neoplasms
Abstract

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance., Significance: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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49. Targeting DNA damage response components induces enhanced STING-dependent type-I IFN response in ATM deficient cancer cells and drives dendritic cell activation.

Author

Lopez-Pelaez M, Young L, Vazquez-Chantada M, Nelson N, Durant S, Wilkinson RW, Poon E, Gaspar M, Valge-Archer V, Smith P, and Dovedi SJ

Subjects
DNA, DNA Damage, Dendritic Cells metabolism, Exodeoxyribonucleases, Indoles, Membrane Proteins genetics, Membrane Proteins metabolism, Morpholines, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Pyrimidines, Sulfonamides, Interferon Type I, Neoplasms genetics
Abstract

The concept of exploiting tumor intrinsic deficiencies in DNA damage repair mechanisms by inhibiting compensatory DNA repair pathways is well established. For example, ATM-deficient cells show increased sensitivity to the ATR inhibitor ceralasertib. DNA damage response (DDR)-deficient cells are also more sensitive to DNA damaging agents like the DNA crosslinker pyrrolobenzodiazepine (PBD) SG-3199. However, additional antitumor benefits from targeting the DDR pathways, which could operate through the activation of the innate immune system are less well studied. DNA accumulation in the cytosol acts as an immunogenic danger signal, inducing the expression of type-I interferon (IFN) stimulated genes (ISGs) by the activation of the cGAS-STING pathway. Here, we demonstrate that ATM -/- FaDu tumor cells have higher basal expression of ISGs when compared to WT cells and respond to ceralasertib and PBD SG-3199 by inducing higher levels of ISGs in a cGAS-STING-dependent manner. We show that sensitive tumor cells treated with ceralasertib and PBD SG-3199 activate dendritic cells (DCs) via a type-I IFN-dependent mechanism. However, STING deficiency in tumor cells does not prevent DC activation, suggesting that transactivation of the STING pathway occurs within DCs. Furthermore, depletion of the cytosolic DNA exonuclease TREX1 in tumor cells increases DC activation in response to PBD SG-3199-treated tumor cells, indicating that an increase in tumor-derived cytosolic DNA may further enhance DC activation. In summary, in this study, we show that ceralasertib and PBD SG-3199 treatment not only intrinsically target tumor cells but also extrinsically increase tumor cell immunogenicity by inducing DC activation, which is enhanced in ATM-deficient cells., Competing Interests: All authors were employees at and stock holders of AstraZeneca at the time of the study., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Published
2022
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50. PARP inhibition is a modulator of anti-tumor immune response in BRCA-deficient tumors.

Author

Staniszewska AD, Armenia J, King M, Michaloglou C, Reddy A, Singh M, San Martin M, Prickett L, Wilson Z, Proia T, Russell D, Thomas M, Delpuech O, O'Connor MJ, Leo E, Angell H, and Valge-Archer V

Subjects
BRCA1 Protein genetics, BRCA1 Protein metabolism, Clinical Trials as Topic, Female, Humans, Immunity, Janus Kinases metabolism, Janus Kinases pharmacology, Janus Kinases therapeutic use, STAT Transcription Factors metabolism, STAT Transcription Factors pharmacology, STAT Transcription Factors therapeutic use, Signal Transduction, Tumor Microenvironment, Ovarian Neoplasms drug therapy, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
Abstract

PARP inhibitors are synthetically lethal with BRCA1/2 mutations, and in this setting, accumulation of DNA damage leads to cell death. Because increased DNA damage and subsequent immune activation can prime an anti-tumor immune response, we studied the impact of olaparib ± immune checkpoint blockade (ICB) on anti-tumor activity and the immune microenvironment. Concurrent combination of olaparib, at clinically relevant exposures, with ICB gave durable and deeper anti-tumor activity in the Brca1m BR5 model vs. monotherapies. Olaparib and combination treatment modulated the immune microenvironment, including increases in CD8+ T cells and NK cells, and upregulation of immune pathways, including type I IFN and STING signaling. Olaparib also induced a dose-dependent upregulation of immune pathways, including JAK/STAT, STING and type I IFN, in the tumor cell compartment of a BRCA1m (HBCx-10) but not a BRCA WT (HBCx-9) breast PDX model. In vitro , olaparib induced BRCAm tumor cell-specific dendritic cell transactivation. Relevance to human disease was assessed using patient samples from the MEDIOLA (NCT02734004) trial, which showed increased type I IFN, STING, and JAK/STAT pathway expression following olaparib treatment, in line with preclinical findings. These data together provide evidence for a mechanism and schedule underpinning potential benefit of ICB combination with olaparib., Competing Interests: All the authors were employees and shareholders of AstraZeneca at the time of this research., (© 2022 AstraZeneca. Published with license by Taylor & Francis Group, LLC.)

Published
2022
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